An important step in obesity research involves identifying neurobiological underpinnings of nonfood reward processing unique to specific subgroups of obese individuals.
Nineteen obese individuals seeking treatment for binge eating disorder (BED) were compared with 19 non-BED obese individuals (OB) and 19 lean control subjects (LC) while performing a monetary reward/loss task that parses anticipatory and outcome components during functional magnetic resonance imaging. Differences in regional activation were investigated in BED, OB, and LC groups during reward/loss prospect, anticipation, and notification.
Relative to the LC group, the OB group demonstrated increased ventral striatal and ventromedial prefrontal cortex activity during anticipatory phases. In contrast, the BED group relative to the OB group demonstrated diminished bilateral ventral striatal activity during anticipatory reward/loss processing. No differences were observed between the BED and LC groups in the ventral striatum.
Heterogeneity exists among obese individuals with respect to the neural correlates of reward/loss processing. Neural differences in separable groups with obesity suggest that multiple, varying interventions might be important in optimizing prevention and treatment strategies for obesity.
Neural reward systems—through their regulation of appetite, weight regulation, and treatment response—have been implicated in obesity (1–3). However, studies in obese populations have demonstrated both hyper- and hyporesponsivity reward neurocircuitry in response to food cues (4–8). These seemingly discordant findings might relate to heterogeneities among obese individuals (9). Obesity is associated with different forms of disordered eating behaviors. For example, groups with obesity and binge eating disorder (BED) differ from those with non-binge-related obesity on numerous behavioral and psychological dimensions (10). A current debate exists with regard to the applicability of “food addiction” to eating behaviors; although some investigators argue a lack of evidence (11), others propose that the construct seems particularly relevant to certain obese subgroups, such as BED (12,13).
Seemingly discordant findings might also reflect failures to adequately disambiguate phases relating to anticipatory and outcome processing (14). Reward anticipation is linked with ventral striatal (VS) activity, whereas greater medial prefrontal cortex activity is associated with reward notification or the outcome phase of reward processing (15–18). Food-cue studies making anticipatory-consummatory distinctions report greater anticipatory responsiveness in the VS, midbrain, amygdala, and thalamus relative to consummatory phases of reward processing in healthy individuals (19,20). Palatable food consumption is associated with greater activity in the orbitofrontal cortex (OFC) and insula, with increased responsiveness observed in obese individuals (19,21,22). In obesity, the anticipatory-consummatory distinction is particularly important, because energy intake seems strongly influenced by anticipatory signaling rather than actual food consumption (23). Heightened anticipation of food reward is posited as a trigger for overeating in obese individuals (20,24).
To date, neuroimaging studies distinguishing anticipatory/ consummatory processing in populations with disordered eating provide complex findings. Obese, relative to lean, individuals show increased activity in the insula and inferior frontal gyrus (IFG) during food anticipation (22). However, in bulimia nervosa, a disorder characterized by binge eating, food anticipation is associated with diminished prefrontal and insula activity, relative to nonbinge-eating individuals (25). Striatal activity is associated with reward processing tasks (15–18,26,27), and altered striatal responses are associated with obesity and weight gain; however, although some studies demonstrate diminished activity after palatable food intake in obese individuals, others report increased striatal responding (6,22,28,29).
Similarly, the addiction literature includes seemingly ambiguous findings in reward processing, even when distinguishing anticipatory/consummatory components. For example, increased striatal activity has been reported in cocaine dependence during anticipatory processing (30), whereas diminished anticipatory VS responses have been noted in alcohol dependence (31) and pathological gambling (32). These differences might relate to specific disorders, methodological/analytical considerations, treatment-seeking status, or anatomical delineations of the VS; additional differences might relate to types of reinforcers (e.g., addiction-related/unrelated).
Although many neuroimaging studies examine reward processes related to food cue paradigms in obese populations, there is a dearth of investigations into non-food reward processing in obesity (33,34). Understanding generalized reward processing in obesity is important, because alterations in reward circuitry might represent vulnerabilities for disordered eating. The current study used functional magnetic resonance imaging (fMRI) to examine monetary reward processing during the anticipation and receipt of wins/losses in obese individuals with and without BED and a lean comparison (LC) group. Binge eating disorder differs significantly from other forms of obesity and eating disorders in numerous behavioral, body-image, psychological, and psychiatric markers (10,35,36). However, to date, only two neuroimaging studies have examined the bio-behavioral correlates of this disorder relative to other obese conditions. The first observed differences in overweight BED participants relative to overweight and lean groups without BED in responses of the ventromedial prefrontal cortex (vmPFC) to food cues (37). Recently, we observed brain activation differences between obese individuals with and without BED during a cognitive control task, with the BED group demonstrating relatively diminished activation in the IFG, vmPFC, and insula (38).
To investigate further differences in obese individuals with and without BED, we employed a widely used monetary incentive delay task (MIDT) to examine reward/loss processing (16,17,32,39,40). We hypothesized that the BED group would show diminished responding in the VS during anticipatory phases, whereas the OB group would demonstrate increased VS activity relative to the LC group. We hypothesized that, consistent with fMRI studies in bulimia (25), during the outcome phase the BED group would demonstrate decreased vmPFC, insula, thalamus, and IFG activity relative to the non-BED groups. Similarities in BED and OB groups were examined, given potential similarities between obese individuals in the neural correlates of reward processing.
Methods and Materials
Participants included 57 adults 19–64 years of age (mean age: 38.9, 34 female), where 64.9% (n = 37) identified as Caucasian, 29.0% (n = 17) identified as African American, 5.3% (n = 3) identified as Native American, and 1.8% (n = 1) identified as Asian American; 5.3% (n = 3) identified themselves as Hispanic, and 94.7% (n = 54) identified as non-Hispanic. Demographic information is in Table 1 and Supplement 1. Age was included as covariates in all group contrast analyses, given group differences in age and to control for potential age-related effects. Body mass index (BMI) in the BED group ranged from 30.1 to 44.1. The OB group included 19 individuals with a BMI ranging from 30.4 to 41.6 and the LC group consisted of 19 individuals with BMIs ranging from 20.4 to 24.6. The BED and OB groups did not differ on mean BMI, and as expected, these groups had higher BMIs than the LC group.
The obese BED group consisted of 19 treatment-seeking participants enrolled in a randomized placebo-controlled trial testing 4-month treatments of sibutramine and cognitivebehavioral-self-help interventions, alone or in combination. Following baseline measures described here, participants underwent the fMRI protocol before starting the treatments, which were delivered for 4 months. The proposed DSM-5 criteria for BED (www.dsm5.org) was used to verify that all individuals in the BED group met criteria, but no individuals in the OB or LC groups had a history or current expression of binge eating or other disordered eating behaviors.
fMRI Acquisition and Analysis
Images were obtained with Siemens TIM Trio 3T MRI systems (Siemens, Malvern, Pennsylvania). Image acquisition and analysis methods are detailed in Supplement 1. Functional images were preprocessed with SPM5 (Welcome Functional Imaging Laboratory, London, UK), normalized to the Montreal-Neurological-Institute template and smoothed with a 6-mm kernel full-width-at-half-maximum. First-level modeling was conducted with robust regression (41) to reduce the influence of outliers (42). Motion and high-pass filter parameters were included as additional regressors of no interest. The Neuroelf analysis package (www.neuroelf.net) was used for second-level random effects analysis. Correction for multiple comparisons was conducted with Monte-Carlo simulation (e.g., AlphaSim), with combined voxel-wise and cluster thresholds to result in a family-wise-error rate of 5%. To examine task-related brain activations, we contrasted: 1) anticipation of monetary gain versus anticipation of no monetary outcome for the prospect (A1) and anticipation of notification (A2) phases (A1Win and A2Win, respectively); 2) anticipation of monetary loss versus anticipation of no monetary outcome for the A1 and A2 phases (A1Loss and A2Loss, respectively); 3) “Win” versus “Neutral” outcome trials (OCWin); and 4) “Loss” versus “Neutral” outcome trials (OCLoss). See Supplement 1 for more information and Balodis et al. (32) depicting trial structure. To examine between-group differences, we compared activity in BED, OB, and LC groups during A1Win, A2Win, OCWin, A1Loss, A2Loss, and OCLoss in pair-wise t tests. In addition to whole-brain contrasts, 2 region-of-interest analyses were performed. These analyses focused on the VS, with coordinates from a meta-analysis of brain circuits recruited during anticipation of monetary incentives (Figure 2) (43) and coordinates encompassing the nucleus accumbens (Figure 3) (26).
The A1 contrast and behavioral and affective response results are located in Supplement 1, given space limitations and the relevance of the A2 and OC phases to addictive processes. Additionally, a conjunction analysis listing overlapping activations across obese groups (BED + OB groups combined) is listed in Table S2 in Supplement 1. All group differences are listed in Table 1. In the following, results highlight and describe group differences related to our hypotheses (i.e., fronto-striatal areas). Results of region-of-interest analyses are depicted in Figures 2 and and33.
OB Versus LC
During A2Win, OB-LC contrasts demonstrated increased activity in the right IFG extending medially to the OFC and in the bilateral thalamus extending to the right caudate, VS (Figure 2C, Figure 3C), and hypothalamus.
During A2Loss, OB–LC contrasts demonstrated increased activity in left IFG extending bilaterally to the right IFG, OFC, and vmPFC; right medial frontal gyrus extending laterally to middle frontal gyrus and IFG; and left midbrain substantia nigra extending medially to red nucleus and lentiform nucleus.
During OCWin, OB–LC contrasts demonstrated relatively decreased activity in the left precentral gyrus extending dorsally to the middle frontal and postcentral gyrus.
During OCLoss, OB–LC contrasts demonstrated diminished activity in the left precentral gyrus extending to the medial frontal and postcentral gyrus.
BED Versus LC
During A2Win, BED–LC contrasts demonstrated relatively increased activity in dorsal caudate extending to middle frontal gyrus, insula, and claustrum and in left cingulate gyrus extending to caudate (Figure 2D). Decreased activity was observed in the dorsal medial frontal gyrus.
During A2Loss, BED–LC contrasts demonstrated relatively increased activity in right caudate extending to IFG. Relatively reduced activity was observed in right middle frontal gyrus extending dorsally to the medial frontal gyrus.
During OCWin, BED–LC contrasts demonstrated relatively diminished activity in right superior temporal gyrus extending to insula, cingulate gyrus, and posterior cingulate; left inferior parietal lobule extending to insula, posterior cingulate, superior/middle temporal gyrus, VS, caudate, postcentral gyrus, precuneus, cuneus, superior/middle occipital gyrus, and culmen; bilateral anterior cingulate extending laterally to right IFG, caudate, and claustrum; bilateral medial frontal gyrus; and right VS.
During OCLoss, BED–LC contrasts demonstrated relatively decreased activity in left precentral gyrus extending to right cingulate gyrus, bilateral anterior cingulate, left paracentral lobule, right postcentral gyrus, and right paracentral lobule; right superior temporal gyrus extending to transverse temporal gyrus, postcentral gyrus, and insula; left insula extending to precentral gyrus and postcentral gyrus; left posterior cingulate extending to lingual gyrus, bilateral precuneus, and cuneus; and right midbrain extending to thalamus and culmen.
BED Versus OB
During A2Win, BED–OB contrasts showed relatively diminished activity in the lentiform nucleus extending bilaterally to the VS (Figure 2B, Figure 3B), hypothalamus, thalamus, caudate, putamen, and midbrain red nucleus; in the right cingulate gyrus extending bilaterally to the medial/superior frontal gyrus; right insula extending to the superior temporal gyrus; and in the left precentral gyrus extending to the IFG.
During A2Loss, BED–OB contrasts demonstrated relatively diminished activity in midbrain red nucleus extending to thalamus, bilateral VS, and substantia nigra; medial frontal gyrus extending to postcentral gyrus, cingulate gyrus, inferior parietal lobule, postcentral gyrus, and superior frontal gyrus; left insula extending to superior temporal gyrus; middle frontal gyrus extending to anterior cingulate and medial frontal gyrus; and left precentral gyrus extending to the postcentral gyrus.
During OCWin, BED–OB contrasts demonstrated relatively diminished activity in insula, lentiform nucleus, para-hippocampal gyrus, cuneus, thalamus, and superior temporal gyrus; right superior temporal gyrus extending to insula, precentral gyrus, and IFG; right medial frontal gyrus extending to anterior cingulate, bilateral VS, and caudate; and left caudate.
During OCLoss, BED–OB contrasts demonstrated no group differences in fronto-striatal regions (Table 1 lists all group differences).
Significant differences were observed between BED, OB, and LC groups in ways that partially confirmed our hypotheses: significant anticipatory differences in the VS were observed during the A2 win/loss phases in BED–OB (but not BED–LC) contrasts; BED–OB comparisons during these phases revealed diminished anticipatory VS responses in BED, whereas OB–LC contrasts showed heightened VS responses in OB. These patterns also held for group differences in the midbrain, thalamus, and amygdala, suggesting differential recruitment of affective and/or motivational circuitry (44,45). Outcome processing in BED participants was associated with diminished prefrontal and insula activity relative to both non-BED groups. The biological and clinical implications are discussed here with respect to differences between group contrasts during anticipatory and outcome reward phases.
Consistent with our hypotheses, anticipatory processing was associated with diminished bilateral VS activity in BED relative to OB participants. Conversely, OB–LC contrasts revealed increased bilateral VS recruitment during this phase in OB participants. Additionally, divergent BED–OB signaling was evidenced in midbrain, amygdala, and thalamus—areas previously identified in food cue paradigms as more responsive during anticipatory relative to consummatory reward processes (19,20). These results, therefore, provide some clarification of seemingly ambiguous hypo- versus hyperactivity reward-processing findings in obesity and underline the importance of differentiating between obesity subtypes and anticipatory-outcome reward phases. The VS, particularly the nucleus accumbens, has been strongly implicated in reward processing, especially as it relates to changes in affective state and goal-directed behaviors (46–48). Our findings of diminished striatal response in the BED group, relative to the OB group, across the A2 win/loss phases accords with MIDT findings in other populations characterized by problems with impulse control, including those with pathological gambling, attention-deficit/hyperactivity disorder, alcohol dependence, and positive family histories for alcoholism (31,32,39,49,50). Similar to pathological gambling–related findings (37), relative frontostriatal hypoactivity in BED participants was less phase-specific than hypothesized. The relatively diminished fronto-striatal activity occurred in both anticipatory and outcome phases and win and loss conditions (Figure 1), indicating in BED a generalized pattern of diminished fronto-striatal processing of rewards and losses. Additionally, BED–LC and BED–OB contrasts produced a similar pattern of differences across the outcome phases on the MIDT, particularly in insular and striatal regions. However, few differences in fronto-striatal regions during the anticipation phase in BED–LC contrasts suggest that the BED group might best be characterized by alterations during outcome phases, whereas the OB group is distinguished through hyperactivity during anticipatory phases.
Relevance to Addiction Theories
Diminished anticipatory processing might represent an important precursor in the development of BED. “Reward deficiency syndrome” posits that individuals with low baseline reward neurocircuitry activity might consume food or engage in addictive behaviors in compensatory efforts to stimulate activity in these areas (51). Altered midbrain responses encompassing the substantia nigra in both the A2W and A2L phases in the BED-OB and the OB–LC contrasts suggest alterations in dopaminergic neural pathways. Indeed, the VS, hypothalamus, thalamus, and prefrontal cortex represent predominant projection areas of the mesocorticolimbic dopamine system, consistent with the role of this neurotransmitter in reward processing (52,53). Although fMRI cannot definitely relate activity changes to dopamine, conjoint fMRI and positron emission tomography studies demonstrate increased dopaminergic activity in prefrontal cortical areas as individuals anticipate and receive monetary rewards (54). Dopaminergic alterations are noted in BED (55–57), and striatal dopamine release during food stimulation is positively associated with dietary restraint (58). Nonetheless, a BED-hypo-active/OB-hyperactive dopaminergic model might oversimplify underlying processes; alterations might relate to specific disorder stages, such that initial hypersensitivity of this system might become downregulated with intermittent overeating of high-fat or sugary foods (59–61). Consistent with the incentive-salience theory, the hedonic impact (i.e., “liking”) of consummatory processing might decrease after over-consumption, whereas the incentive-salience (i.e., “wanting”) component is heightened. In the current study, BED participants demonstrated diminished anticipatory processing relative to the OB group to monetary cues; it is possible that exposure to food cues (i.e., disorderspecific stimuli) might increase activity in fronto-striatal networks (37).
In contrast to the BED group, OB–LC group differences were mostly contained within the anticipatory phases. Findings in the OB (relative to LC) group of increased medial/lateral OFC, striatum, amygdala, and hippocampal activation during anticipatory processing are consistent with similar response patterns noted during presentation of food cues (7) and support the idea of greater reward anticipation in this group.
Consistent with our hypotheses, BED participants demonstrated relatively diminished activity in prefrontal and insular regions during outcome phases, relative to both OB and LC groups. These findings are consistent with reports in full and subthreshold bulimia, where individuals demonstrate diminished activity in left middle frontal gyrus, insula, and right precentral gyrus during palatable food consumption (25). Additionally, vmPFC and right insula atrophy are linked to compulsive binge-eating etiology (62). In both BED–OB and BED–LC contrasts, diminished bilateral insula activity extending to the IFG is evident in BED participants. The insula constitutes the primary taste cortex but is also implicated in homeostatic signaling (63–65). Therefore, the results support the idea of altered generalized reward processing in BED. Altered interoceptive awareness through blunted insula activity, particularly during outcome processing, suggests an impaired ability to integrate reward information relating to the current state of the individual. Additionally, the IFG is implicated in the interaction between cognitive and motivational processing during inhibitory control (66–68); therefore collective diminished IFG and insula signaling might have implications for gauging hunger/satiety signals.
Strengths, Limitations, and Future Directions
To our knowledge, the current study is the first fMRI investigation into generalized reward processing across distinctive reward phases and between obesity subgroups, including those with BED. The application of a reward-processing paradigm in obese groups displaying different eating behaviors provides greater insight into potential biomarkers of each phenotype. In this way, the current study parses specific neural correlates related to eating-behavior patterns from those associated with obesity. Additionally, the fMRI task provides the opportunity to examine neurofunctional patterns associated with reward/loss processes that might promote specific eating patterns.
The current study is limited by several factors. The low number of male participants in the BED group precluded an examination of gender differences; administration of eating questionnaires across all groups might also have identified other important eating characteristics. Previous studies have reported differences related to BED severity in clinical versus community samples (69); therefore, it is possible that the treatment-seeking nature distinguished the BED from the OB and LC groups. Some of the whole-brain findings do not survive a conservative Bonferroni correction for multiple comparisons relating to the six phases of the MIDT and the three diagnostic groups examined.
Future research could further examine commonalities between BED and OB groups; in the current study conjunction analyses identified overlap in more dorsal and posterior areas (Table S2 in Supplement 1). Additionally, little overlap was observed between obese groups in the BED–LC and OB–LC contrasts. Concordant areas appeared mostly during outcome phases and in more dorsal posterior regions, including diminished posterior cingulate, precuneus, and precentral gyrus activity during both outcome phases. These areas are implicated in reward expectation and the control of attention; for example, the posterior cingulate is ascribed a role in signaling environmental change, including reward outcome, with increased activity corresponding with changes in internal state or environmental variables (70). Diminished activity in these areas in the obese groups suggests alterations in attention and motivation during feedback in the outcome phases.
Future studies should also examine possible differences related to gender, smoking status, and treatment-seeking behaviors in obese individuals. Another important step will involve understanding how these neural systems interact with homeostatic mechanisms (71,72) and additionally relate these to the chronicity/duration of obesity and/or BED. Longitudinal studies could further provide temporal links between weight changes and reward system processing and identify biological markers related to food intake preceding obesity development. Although the current experimental design cannot discriminate whether these differences are a cause or consequence of obesity or binge eating, they nonetheless have significant implications for the treatment of obesity. Therapies focused on stimulating corticostriatal limbic activity might represent important treatment strategies for BED. More broadly, these findings suggest the potential relevance of health policies in regulating high-fat, high-sugar foods that might alter reward responsivity in those at risk for binge eating and obesity (73).
The current study represents an important step in examining groups of people with obesity and brain correlates of non-food reward processing. Findings of reduced cortico-striatal processing in BED participants across anticipatory and outcome reward phases relative to OB and LC groups suggest reduced recruitment of networks involved in reward processing and selfregulation. These data also provide evidence of similar neurocircuitry alterations mediating reward processing in other disorders of impulse control, such as pathological gambling and alcohol dependence. The inclusion of both BED and OB groups represents a key step in considering how complex behaviors contribute to obesity. Altogether, the current findings suggest divergent neural substrates in abstract reward processing distinguishing specific subgroups of obese individuals. These data might provide insight into seemingly ambiguous findings of VS activity in obesity research.
Support was provided by the following grants: National Institutes of Health (NIH) grants R01-DA019039, P20-DA027844, P50-AA012870, R01-DA020908, R01-AA016599, RL1-AA017539, K12-DA00167, R01 DK073542, PL1-DA024859, and 2K24 DK070052. We gratefully acknowledge Scott Bullock, Jessica Montoya, Naaila Panjwani, Monica Solorzano, Jocelyn Topf, Katie VanBuskirk, Rachel Barnes, and Robin Masheb for their help with the project. The contents of the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of any of the funding agencies.
Dr. Potenza has consulted for and advised Boehringer Ingelheim; consulted for and has financial interests in Somaxon; received research support from the NIH, Veterans Administration, Mohegan Sun Casino, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, Forest Laboratories, Psyadon, Ortho-McNeil, Oy-Control/Biotie, and GlaxoSmithKline pharmaceuticals; participated in surveys, mailings, or telephone consultations related to drug addiction, impulse control disorders, or other health topics; consulted for law offices and the federal public defender’s office in issues related to impulse control disorders; provides clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; performed grant reviews for the NIH and other agencies; given academic lectures in grand rounds, continuing medical education events, and other clinical or scientific venues; and generated books or book chapters for publishers of mental health texts.
All other authors report no biomedical financial interests or potential conflicts of interest.
Supplementary material cited in this article is available online at http://dx.doi.org/10.1016/j.biopsych.2013.01.014.